The pressure to fudge medical research findings

The peer review process for identifying anomalies in research before it is published is clearly failing.

dra_schwartz: istockphoto

The medical research community has uncovered a worrying trend: why are large numbers of medical researchers apparently misrepresenting their findings? Sophie Scott investigates.

Australia has a proud tradition of being a world leader when it comes to medical breakthroughs.

Think of the 'bionic ear', the cervical cancer vaccine and the Nobel prize-winning discovery of Helicobacter pylori, just to name a few.

These discoveries have had world-wide impact and saved thousands of lives.

While there is much to be proud of, when it comes to biomedical research there appears to be a disturbing trend in Australia.

Three major Australian universities are currently investigating serious allegations of alleged research misconduct.

The claims range from possibly manipulated images, falsified data to - unbelievably - allegations that a study with published results never actually took place.

How is this possible, with the systems of checks and balances within universities and the international peer review process for published research?

The ABC has detailed new allegations about alleged research misconduct at one of Australia's leading universities.

The University of New South Wales is already embroiled in a long-running inquiry into research overseen by professor Levon Khachigian, the scientist behind a cancer compound called DZ13. Now they're investigating whether images in a scientific paper he co-authored last year on cardiovascular disease were duplicated.

Findings in 90 per cent of the important cancer papers published in significant medical journals could not be replicated.

The latest allegations centre on a scientific paper looking at how smooth muscle cells change into plaque, a key cause of heart attacks.

The UNSW is investigating a paper co-authored by Professor Khachagian published in a scientific journal PlosOne last year.

The core of the complaint is whether images in the scientific paper were manipulated. One image appears to have been rotated to show a different result.

In an email to the ABC Professor Khachigian says it was a genuine error and says he's never engaged in research misconduct.

It's not the first accusation levelled at research overseen by Professor Khachigian. In August this year, the ABC detailed serious concerns about research into a cancer compound DZ13. The drug had been tested on a small group of skin cancer patients and was about to be trialled on people with melanoma.

But with growing concerns about the science, the tests were suspended pending the outcome of the university's inquiries. The investigation is still on-going.

In another case this year, it appears that a patient-based study wasn't even conducted, despite positive 'results' being published.

At the University of Queensland, senior management was forced to return a grant of $20,000 from Parkinsons Australia and retract a scientific paper co-written by former staffer Professor Bruce Murdoch, from the Centre for Neurogenic Communication Disorders Research.

The university discovered that a study into trans cranial magnetic stimulation for Parkinson's disease may not have actually been carried out.

"No primary data can be located and no evidence has been found that the study described in the article was conducted," according to the University of Queensland.

A paper on the study was published online in 2012 in the European Journal of Neurology which was subsequently retracted. The University is still investigating the matter.

A further case concerns a wound healing cream developed at the Queensland Institute of Technology.

Luke Cormack was a PhD student who alerted a scientific journal about what he believes are inconsistencies in research on growing human embryonic stem cells in the laboratory. While an internal investigation cleared researchers involved of misconduct, there are now claims that research grants may have been paid upon the basis of false information.

The National Health and Medical Research Council has referred the matter to the Australian Research Integrity Committee, a body which can look into procedural matters regarding research integrity.

In Australia, scientists are governed by the Australian Code on the Responsible Conduct of Research. Any allegations of research misconduct are investigated directly by the universities or institutions involved.

While it may convene an external enquiry panel to look into any prima facie case of research misconduct, it's still the university itself which has a final say on penalties. What Australia needs, according to Professor David Vaux, from the Walter and Eliza Hall Institute, is an independent office for research integrity or an ombudsman, to advise institutions and handling allegations of misconduct.

He proposes a model similar to the United States office for research integrity which handles hundreds of research allegations each year.

He says having an independent umpire, removed from universities and research institutions, would ensure matters could be handled fairly. Without an independent office like that, it's difficult to know just how widespread research misconduct is. But around the world, there is an increasing focus on re-testing accepted findings to check their veracity.

In a commentary published in journal Nature in 2012, scientists from biotech company Amgen found that findings in 90 per cent of the important cancer papers published in significant medical journals could not be replicated, even with the help of original scientists.

In another review, scientists at the pharmaceutical company Bayer looked back at 67 scientific projects, covering the majority of Bayer's work in oncology, women's health and cardiovascular medicine over the past four years. Of these, they found results from internal experiments matched up with the published findings in only 14 projects, but were highly inconsistent in 43 (in a further 10 projects, claims were rated as mostly reproducible, partially reproducible or not applicable.)

"People take for granted what they see published," John Ioannidis, an expert on data reproducibility at Stanford University School of Medicine in Palo Alto, California wrote in Nature in Sep 2011. "But this and other studies are raising deep questions about whether we can really believe the literature, or whether we have to go back and do everything on our own."

While some of the un-reproducable results could be due to sloppy research, it appears that much of it is a result of deliberate misconduct. This was clear from a paper published last year.

Dr Ferris C Fang conducted a detailed review of all 2,047 biomedical and life-science research articles indexed by PubMed as retracted on May 3, 2012. It revealed that only 21.3 per cent of retractions were attributable to error.

Dr Fang's findings were published in the Proceedings of the National Academies of Science in 2012. It revealed that 67.4 per cent of retractions were attributable to misconduct, including fraud or suspected fraud (43.4 per cent), duplicate publication (14.2 per cent), and plagiarism (9.8 per cent).

"Incomplete, uninformative or misleading retraction announcements have led to a previous underestimation of the role of fraud in the ongoing retraction epidemic," he wrote. "The percentage of scientific articles retracted because of fraud has increased 10-fold since 1975."

The reasons why some scientists might engage in research misconduct remain unclear but it's likely that multiple factors are at play.

With scientists constantly having to compete for precious research grants, the pressure to come up with successful findings is intense. To prosper, scientists need to publish as many papers as possible, ideally in well-respected journals.

Dr Fang told the New York Times in April 2012, that "the scramble to publish in high impact journals may be leading to more and more errors".

And the peer review process for identifying anomalies in research before it is published is clearly failing.

So much so, that in August 2010 two medical reporters, based in the United States, set up a website called Retraction Watch.

Since Adam Marcus and Ivan Oransky launched RetractionWatch, they say it's been a struggle to even keep up with retractions as they happen. Marcus is the managing editor of Anesthesiology News, a monthly magazine for anaesthetists. Oransky is the vice president and global editorial director of MedPage

Today and teaches medical journalism at New York University's Science, Health, and Environmental Reporting Program. So far, their blog has analysed more than 250 retractions in nearly 350 posts since its launch.

RetractionWatch averages 150,000 page views a month with around six posts about retracted papers each week, something the web sites creators did not expect when they set it up.

Reducing the incidence of research misconduct will not be easy. With all the checks and balances in place, there could be some willing to cut corners, and rejig findings to gain some advantage. The challenge is making it as difficult as possible for that happen.